Kutoh Eiji, Wada Asuka, Murayama Teruma, Hayashi Jyunka
Division of Clinical Research, Biomedical Center, Tokyo, Japan.
Department of Internal Medicine, Division of Endocrinology and Metabolism, Gyoda General Hospital, Saitama, Japan.
Indian J Endocrinol Metab. 2018 Mar-Apr;22(2):185-190. doi: 10.4103/ijem.IJEM_578_17.
The aim of this project is to compare the effect of canagliflozin monotherapy on metabolic parameters between responders and nonresponders with this drug. This study is a prospective, unblinded, observational study.
Drug-naïve patients with type 2 diabetes mellitus received only 50-100 mg/day canagliflozin for 3 months ( = 39). They were divided into two groups according to the novel "A1c index" to assess glycemic efficacies; responders ( = 24) and nonresponders ( = 15).
At baseline, glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) were significantly higher and homeostatic model assessment (HOMA)-B and body mass index (BMI) were significantly lower in responders. In both groups, similar, significant reductions of BMI (-1.9% with responder and -1.8% with nonresponder) and HOMA-R (-35.8% for responder and -31.5% for nonresponder) were observed. However, differences were seen with other parameters as follows: 1) responders: significant reductions of HbA1c (10.95%-8.44%), FBG (-29.6%) or free fatty acid (FFA) (-16.2%), and significant increases of HOMA-B (79.7%) were observed. 2) Nonresponders: significant reductions of serum uric acid (UA) (-8.6%) levels were seen. Significant correlations were observed between the baseline levels of serum UA and those of HOMA-B ( = 0.7259). However, this link became uncorrelated with the treatment with canagliflozin.
These results suggest that (1) responders with canagliflozin have lower BMI and beta-cell function. Reductions of body weight with canagliflozin were not associated with its glycemic efficacy, (2) reduced FFA levels and enhanced insulin sensitivity/beta-cell function could be a potential mechanism of good glycemic efficacy of canagliflozin, and (3) serum UA might be involved in modulating beta-cell function during canagliflozin treatment.
本项目旨在比较卡格列净单药治疗对该药物反应者与无反应者代谢参数的影响。本研究为前瞻性、非盲、观察性研究。
初治2型糖尿病患者仅接受每日50 - 100 mg卡格列净治疗3个月（n = 39）。根据新的“A1c指数”将他们分为两组以评估血糖疗效；反应者（n = 24）和无反应者（n = 15）。
基线时，反应者的糖化血红蛋白（HbA1c）和空腹血糖（FBG）显著更高，而稳态模型评估（HOMA）-B和体重指数（BMI）显著更低。两组中，均观察到BMI（反应者降低1.9%，无反应者降低1.8%）和HOMA-R（反应者降低35.8%，无反应者降低31.5%）有相似的显著降低。然而，其他参数存在差异如下：1）反应者：观察到HbA1c（从10.95%降至8.44%）、FBG（降低29.6%）或游离脂肪酸（FFA）（降低16.2%）显著降低，以及HOMA-B显著升高（升高79.7%）。2）无反应者：血清尿酸（UA）水平显著降低（降低8.6%）。观察到血清UA基线水平与HOMA-B基线水平之间存在显著相关性（r = 0.7259）。然而，这种联系在卡格列净治疗后变得不相关。
这些结果表明，（1）卡格列净反应者的BMI和β细胞功能较低。卡格列净导致的体重减轻与其血糖疗效无关，（2）FFA水平降低以及胰岛素敏感性/β细胞功能增强可能是卡格列净良好血糖疗效的潜在机制，并且（3）血清UA可能参与卡格列净治疗期间β细胞功能的调节。
